US3717658A - 3'-arylspiro(imidazolidine-2,1'-phthalan)and 2-(2'-(alpha-hydroxy-arylmethyl)-aryl)-2-imidazoline derivatives - Google Patents

3'-arylspiro(imidazolidine-2,1'-phthalan)and 2-(2'-(alpha-hydroxy-arylmethyl)-aryl)-2-imidazoline derivatives Download PDF

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US3717658A
US3717658A US00711202A US3717658DA US3717658A US 3717658 A US3717658 A US 3717658A US 00711202 A US00711202 A US 00711202A US 3717658D A US3717658D A US 3717658DA US 3717658 A US3717658 A US 3717658A
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compounds
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imidazoline
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W Metlesics
L Sternbach
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F Hoffmann La Roche AG
Hoffmann La Roche Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
    • C07C45/29—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation of hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/41—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by hydrogenolysis or reduction of carboxylic groups or functional derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/20—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D233/22—Radicals substituted by oxygen atoms

Definitions

  • the invention relates to 3'-arylspiro[imidazolidine-Z,1'- phthalan] and 2 [2' (a-hydroxy-arylmethyD-aryl]-2- imidazoline derivatives. More particularly, the invention relates to compounds of the formulae wherein R R R and R are each independently selected from the group consisting of hydrogen, halogen, lower alkyl, lower alkoxy, hydroxy and trifiuoromethyl; R and R are each independently selected from the group consisting of hydrogen and lower alkyl, and pharmaceutically acceptable acid addition salts thereof.
  • the compounds of Formulae I and II are useful as antidepressant agents.
  • the invention relates to compounds wherein R R R and R are hydrogen or to compounds wherein R R and R are hydrogen.
  • the invention relates to a process exemplified by the following reaction scheme:
  • the invention relates to a process exemplified by the following reaction scheme:
  • the invention relates to comwherein R R R R and R are each independently selected from the group consisting of hydrogen, halogen, lower alkyl, lower alkoxy, hydroxy and trifluoromethyl; and R and R are each independently selected from the group consisting of hydrogen and lower alkyl, which can undergo a prototropic shift to form compounds of the formula B4 II wherein R R R R R and R each have the same 4 meaning as hereinabove, and pharmaceutically acceptable acid addition salts thereof. Both tautomeric isomers as well as mixtures thereof are within the scope of the invention.
  • the compounds of Formula 111 can also undergo a prototropic shift to form compounds of Formula IV.
  • the compounds of Formula III are converted to the compounds of Formula I and its tautomers utilizing a reducing agent such as, sodium borohydride, hydrogen, in the presence of Raney nickel, zinc in ethanol and the like.
  • a reducing agent such as, sodium borohydride, hydrogen
  • the reduction is suitably carried out at room temperature or above, preferably at a temperature between about 20 C. and C.
  • the reduction can be suitably carried out in the presence of an inert organic solvent such as, for example, dimethylformamide; hydrocarbon solvents such as benzene, toluene; alkanols such as, methanol, ethanol and the like.
  • the hydroxyl proton of a compound of Formula II can undergo a prototropic shift to form the corresponding isomeric end product of Formula I.
  • the product obtained upon reduction of a compound of Formula III will ordinarily be a mixture of the tautomeric forms I and H.
  • the relative amounts of the isomeric forms present is dependent upon such factors as the solvent system employed, the pH of the medium and the particular product, i.e., the meaning of R R R R R and R in Formulae I and II.
  • the intermediates of Formula VI are readily condensed with diamines of the formula wherein R and R have the same meaning as hereinabove by mixing the components or by reacting them in the presence of an organic solvent such as benzene, toluene; alcohols such as lower alkanols and the like.
  • the condensation is conveniently carried out at room temperature or above, preferably at a temperature between about 20 C. and 150 C.
  • the diamine reactant of Formula VIII can be employed as a salt thereof in which case the reaction is conducted by heating the mixture of reactants to a melt.
  • reaction products i.e., the compounds of Formula VIII can be readily oxidized, for example, by treatment with an oxidizing agent such as hydrogen peroxide or by exposure to gaseous oxygen at room temperature to give the peroxides of Formula IX which are readily reduced to the corresponding end products.
  • an oxidizing agent such as hydrogen peroxide or by exposure to gaseous oxygen at room temperature to give the peroxides of Formula IX which are readily reduced to the corresponding end products.
  • the oxidation is conveniently carried out in an organic solvent such as alcohols, dimethylformamide, etc. at room temperature. Higher or lower temperatures, e.g., between about 20 C. and 100 C., can also be employed.
  • the reaction mixture obtained upon treatment of a compound of Formula VIII with an oxidizing agent will ordinarily contain the end products along with the peroxide intermediate of Formula IX.
  • Complete reduction of the peroxide can be accomplished without separating it from the reaction mixture and, in a preferred embodiment, the om'dation product is submitted directly to treatment with a reducing agent.
  • the peroxide intermediate of Formula IX can be separated from the reaction mixture obtained upon treatment of a compound of Formula VIII with an oxidizing agent by any of the usual techniques, e.g., chromatographic separation, fractional crystallization, etc.
  • the reduction of the peroxide is conveniently carried out by employing any reducing agent conventionally used for the reduction of peroxides such as sodium sulfite, trialkylphosphite, etc., preferably in the presence of an organic solvent such as an alcohol, e.g., methanol, ethanol, etc.; dimethylformamide and the like, or when using a salt of the peroxide, the reduction can be carried out in an aqueous solvent, e.g., in an aqueous alcoholic solvent.
  • the reduction is suitably carried out at room temperature or above, preferably at a temperature between about 20 C. and 100 C.
  • the hydroxyl proton of a compound of Formula IV can undergo a prototropic shift to form the corresponding isomeric end product of Formula III.
  • the product obtained upon oxidation and reduction of an intermediate of Formula VIII will ordinarily be a mixture of the tautomeric forms III and IV.
  • the relative amounts of the isomeric forms present is dependent upon such factors as the solvent system employed, the pH of the medium and the particular product, i.e., the meaning of R R R R R and R in Formulae III and IV.
  • the product obtained upon oxidation and reduction of 2,3-dihydro 5 phenyl-5H-imidazo[2,1-a]isoindole contains a mixture of the tautomers 2,3-dihydro-5-hydroxy-5-phenyl- SH-imidazo[2,l-a1isoindole and 2-(2-benzoylphenyl)-2- irnidazoline, in a ratio of about 1:1.
  • the acid addition salts isolated in the ordinary manner from the reaction product of the oxidation and reduction of 2,3-dihydro-5- phenyl- SH- imidazo[2,1-a]isoindole are ordinarily obtained as structure III.
  • B is an alkylene chain of 2 to 4 carbon atoms in which one or more of the hydrogens can be replaced by lower alkyl, preferably B is iiaih wherein R and R are each independently hydrogen or lower alkyl, and X is a halogen such as chlorine, bromine or iodine.
  • the compounds of Formula IX can be converted to the compounds of Formula X, utilizing a halogenating agent, for example, halogen, such as chlorine, bromine or iodine, N-bromosuccinimide, N- chlorosuccinimide and the like.
  • a halogenating agent for example, halogen, such as chlorine, bromine or iodine, N-bromosuccinimide, N- chlorosuccinimide and the like.
  • the compounds of Formula X can readily be condensed with diamines of the formula wherein B is as previously described, by mixing the components or by reacting them in the presence of an inert organic solvent, for example, ethcrs, hydrocarbons, such as benzene, toluene; alcohols, such as lower alkanols and the like.
  • an inert organic solvent for example, ethcrs, hydrocarbons, such as benzene, toluene; alcohols, such as lower alkanols and the like.
  • the condensation is conveniently carried out at room temperature or above, preferably at a temperature between about 20 C. and C.
  • the diamine reactant of Formula XI can be employed as a salt thereof in which case the reaction is conducted by heating the mixture of reactants to a melt.
  • the compounds of Formula IX are known compounds or can be prepared in an analogous manner to known compounds.
  • Suitable salts of the compounds of Formulae I and III and their tautomers are prepared from non-toxic organic and inorganic acids.
  • Suitable organic acids are, for example, maleic acid, fumaric acid, ascorbic acid, tartaric acid, salicyclic acid, succinic acid, citric acid and the like.
  • Suitable inorganic acids are, for example, the hydrohalic acids, e.g., hydrochloric acid and hydrobromic acid; sulfuric acid, sulfamic acid, phosphoric acid, etc.
  • the acid addition salts are readily prepared by the usual techniques for the preparation of acid addition salts which are readily apparent to those skilled in the art.
  • the compounds of Formula I and their tautomers are useful intermediates for the preparation of compounds of Formula 'III and their tautomers.
  • the compounds of Formula I, their tautomers and their pharmaceutically acceptable acid addition salts are also useful as psychostimulants.
  • the compounds of Formula I and its tautomers can be converted to the compounds of the Formula VIII utilizing as a catalyst a strong base or acid, such as boron trifluoride, sodium hydride, alkali metal alkoxides, preferably lower alkoxides and the like.
  • a strong base or acid such as boron trifluoride, sodium hydride, alkali metal alkoxides, preferably lower alkoxides and the like.
  • the rearrangement is suitably carried out at room tem perature or above, preferably at a temperature between about 20 C. and 100 C.
  • the rearrangement can be suitably carried out in the presence of an inert organic solvent, such as, for example, dimethylformamide, dimethylsulfoxide; hydrocarbon solvents, such as benzene and toluene; chlorinated hydrocarbons, such as chloroform; and alkanols, such as methanol, ethanol and the like.
  • an inert organic solvent such as, for example, dimethylformamide, dimethylsulfoxide
  • hydrocarbon solvents such as benzene and toluene
  • chlorinated hydrocarbons such as chloroform
  • alkanols such as methanol, ethanol and the like.
  • the compounds of Formula VIII can be converted to the compounds of Formula IV and its tautomers utilizing an oxidizing agent, such as hydrogen peroxide or by exposure to gaseous oxygen at room temperature.
  • an oxidizing agent such as hydrogen peroxide or by exposure to gaseous oxygen at room temperature.
  • the oxidation is conveniently carried out in an inert organic solvent, for example, alcohols, ethers, dimethylformamide, chlorinated hydrocarbons, hydrocarbons, and the like, at room temperature. Higher or lower temperatures, e.g., between about 20 C. and 100 C. can also be employed.
  • the diol starting materials of Formula V are known compounds or are readily obtainable in analogy to the preparation of the known compounds.
  • the diol starting materials can be readily converted to the dicarbonyl intermediates of Formula VI by oxidation techniques which are known per so such as, for example, using selenium dioxide and the like, as the oxidizing agent or by employing other oxidizing systems such as chromium trioxide in pyridine.
  • Treatment with an oxidizing agent can be conveniently carried out in an organic solvent such as, for example, dimethylformamide, dimethylsulfoxide; hydrocarbon solvents such as benzene, toluene; alkanols, e.g., the lower alkanols, methanol, ethanol, etc.; acetic acid and the like.
  • the oxidation reaction is preferably carried out at an elevated temperature suitably at a temperature between about room temperature and about C.
  • mice 2-[2-(a-hydroxybenzyl)-phenyl]-2-imidazoline prevented the ptosis induced by tetrabenazine at 7 mg./ kg. (Pletscher et al., Progress. Drug Research, vol. II, page 417, 1960).
  • the compounds of Formula III their tautomers and their pharmaceutically acceptable acid addition salts are useful as psychostimulants.
  • the compound 2- (2-benzoylphenyl)- Z-imidazoline which has demonstrated an LD in mice of, for example 200 mg./kg. p.o.; 130 mg./kg. s.c.; 77 mg./kg. i.p.; and 37 mg./kg. i.v. (Proc. Soc. Exptl. Biol. Med., vol.
  • the activity of the compounds of Formula IV first demonstrated by pharmacological evaluation in warm-blooded animals as indicated herein permits their use in therapy in the same general manner as imipramine or amphetamine, which latter compounds exhibit psychostimulant activity in the DOPA potentiation test at doses of mg./ kg. ip and 1.0 mg./kg. i.p., respectively, and in the ptosis prevention test at doses of 60 mg./kg. and 7.5 mg./kg., respectively.
  • the compound 2,3,4,5-tetrahydro 7 hydroxy-7-phenyl-7H-diazepino[2,1-a]isoindole which has demonstrated an LD of, for example, 40 mg./kg. i.v., prevented the ptosis induced by tetrabenazine at 0.4 mg./kg. p.o.; reversed the hypothermia and hypometabolic effects induced by reserpine (10 mg./kg. s.c.) in mice at 25 mg./kg. p.o.; and potentiated the effects of DOPA in mice at a dose of 7.5 mg./kg.
  • the compounds of Formula III and IV thus demonstrate a pattern of activity associated with antidepressants of known clinical efficacy and are similarly useful as psychostimulants in the treatment of depressed states, for example, in cases of simple depression or in cases of chronic nervous exhaustion.
  • the compounds of Formula III and their tautomers are disclosed in copending application Ser. No. 639,315, filed May 18, 1967.
  • novel end products of this invention i.e., the compounds of Formula I and their tautomers, as well as the compounds of Formula III and their tautomers, are mostly white crystalline odorless solids melting at temperatures in the order of 50-250 C. They have basic properties and can be conveniently prepared in the form of their acid addition salts. Suitable salts are prepared as described hereinabove. The salts are characteristically white crystalline odorless solids.
  • the compounds of Formula I, as well as the compounds of Formula III, preferably in the form of their acid addition salts, can be formulated into preparations suitable for administration by enteral or parenteral routes. They can be embodied in pharmaceutical unit dosage containing from about 0.5 mg. to about mg. of active material, i.e., a compound of Formulae I or III or a salt thereof. Parenteral formulations will ordinarily contain less of the active substance than compositions intended for enteral, e.g., oral administration.
  • the products of this invention can be prepared as tablets, capsules and the like containing about 10 to 50 mg. of active material.
  • Formulations suitable for oral administration may be such as to provide either immediate, or in the alternative, sustained release of the active drug.
  • the formulations will be prepared with pharmaceutically acceptable adjuvant materials comprising from about 60 to about 98 percent of the weight of the compositions in oral dosage form.
  • the compounds can be formulated with a liquid diluent, for example, distilled Water, in the preparation of a suitable parenteral dosage form.
  • a liquid diluent for example, distilled Water
  • the preferred parenteral dosage form will contain from about .5 mg. to about 15 mg. of the active drug.
  • the compounds of this invention are formulated with conventional inert adjuvants into dosage forms suitable for enteral or parenteral administration following the conventional techniques and procedures of the prior art.
  • Suitable dosage forms include tablets and capsules as well as solutions, emulsions and suspensions
  • the inert adjuvants which are suitable for use in preparing the various dosage forms include liquids and solids, inorganic or organic in nature, such as Water, gelatin, lactose, starch, magnesium stearate, talc, vegetable oils, gums, polyalkylene glycols, Vaseline, etc.
  • the compounds can be used in combination with preservatives, stabilizers, Wetting or emulsifying agents salts for altering the osmotic pressure, buffers, etc. If desired, the compound can be used also in admixture with other therapeutically valuable substances. Specific embodiments showing illustrative formulations of an exemplary compound of Formula III follow.
  • the drug in the preferred oral dosage form i.e., tablets or capsules containing 10 to 25 mg. of active material
  • the parenteral composition will be administered ordinarily one or two times daily.
  • Effective dosages for the administration of compounds of this invention i.e., the compounds of Formulae I and II, as well as compounds of Formulae Ill and IV will, of course, depend in all instances upon the severity and individual characteristics of each case as determined by the prescribing practitioner. It will be understood that dosage forms containing larger and smaller quantities of the active drug ingredient are encompassed by the scope of this invention and that such dosage forms can be administered more or less frequently than indicated heretofore. It will be understood that dosage forms containing inert adjuvants in quantities which are greater or less than those indicated heretofore are also encompassed by this invention.
  • the 2- (2-benzoylphenyl)-2-imidazoline prepared in this manner can form the isomeric 2,3-dihydro-5-phenyl- 5H-imidazo[2,1-a]isoindol-5-ol.
  • the hydrobromide was prepared by adding an aqueous solution of hydrobromic acid to a suspension of 2-(2- benzoylphenyl)-2-imidazoline in ethanol. Addition of ether gave a precipitate which after recrystallization from a mixture of ethanol and ether gave white platelets melting at 193-194 dec.
  • a compound of the formula 5 H EH or its tautomer NH- Ra (IJHOH wherein R and R are each independently selected from the group consisting of hydrogen, halogen, lower alkyl, lower aLkoxy, hydroxy and trifluoromethyl and R and R are each independently selected from the group consisting of hydrogen and lower al-kyl of 1-7 carbon atoms or a pharmaceutically acceptable acid addition salt thereof.
  • R and R are hydrogen, i.e., 3-phenylspiro[imidazolidine-Z,lphthalan] or its tautomer.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Indole Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Plural Heterocyclic Compounds (AREA)
US00711202A 1968-03-07 1968-03-07 3'-arylspiro(imidazolidine-2,1'-phthalan)and 2-(2'-(alpha-hydroxy-arylmethyl)-aryl)-2-imidazoline derivatives Expired - Lifetime US3717658A (en)

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US (1) US3717658A (enrdf_load_stackoverflow)
JP (1) JPS4843757B1 (enrdf_load_stackoverflow)
AT (2) AT282623B (enrdf_load_stackoverflow)
BE (2) BE729433A (enrdf_load_stackoverflow)
BR (2) BR6906858D0 (enrdf_load_stackoverflow)
CA (1) CA948638A (enrdf_load_stackoverflow)
CH (2) CH503045A (enrdf_load_stackoverflow)
DE (2) DE1910932A1 (enrdf_load_stackoverflow)
ES (2) ES364424A1 (enrdf_load_stackoverflow)
FR (2) FR2003407A1 (enrdf_load_stackoverflow)
GB (2) GB1185618A (enrdf_load_stackoverflow)
HU (2) HU162976B (enrdf_load_stackoverflow)
IE (2) IE33111B1 (enrdf_load_stackoverflow)
IL (3) IL31558A (enrdf_load_stackoverflow)
NL (2) NL6902846A (enrdf_load_stackoverflow)
NO (2) NO126084B (enrdf_load_stackoverflow)
SE (1) SE347511B (enrdf_load_stackoverflow)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3852303A (en) * 1969-03-05 1974-12-03 Sandoz Ag PROCESS FOR IMIDAZO{8 2,1-a{9 ISOINDOLES AND INTERMEDIATES
US3879415A (en) * 1967-03-30 1975-04-22 Hoffmann La Roche Novel 2{8 2-(1,3-diazacycloalk-2-enyl){9 benzophenone derivatives and novel 1,3-diazacycloalkenyl {8 2,1-a{9 {0 isoindole derivatives
US3931218A (en) * 1973-02-14 1976-01-06 American Home Products Corporation 2-(N-alkyl-2-imidazolin-2-yl)benzophenones and process for their preparation
US3935218A (en) * 1968-09-05 1976-01-27 American Home Products Corporation Imidazolinyl phenyl carbonyl compounds acid addition salts and related compounds
US3936471A (en) * 1974-08-07 1976-02-03 American Home Products Corporation (Hexahydrobenzimidazol-2-yl)benzophenones and derivatives
US3992400A (en) * 1974-04-04 1976-11-16 The Upjohn Company 1-(α-Phenyl-o-tolyl)imidazoles

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH531511A (de) * 1969-03-05 1972-12-15 Sandoz Ag Verfahren zur Herstellung des N,o-Dilithium-Derivats von 2-Phenyl-2-imidazolin
JPS53151759U (enrdf_load_stackoverflow) * 1977-05-07 1978-11-29

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3888846A (en) * 1967-03-30 1975-06-10 Hoffmann La Roche Process for 2(2-(1,3-diazacycloalk-2-enyl))benzophenone derivatives and 1,3-diazacycloalkenyl(2,1-a)isoindole derivatives

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3879415A (en) * 1967-03-30 1975-04-22 Hoffmann La Roche Novel 2{8 2-(1,3-diazacycloalk-2-enyl){9 benzophenone derivatives and novel 1,3-diazacycloalkenyl {8 2,1-a{9 {0 isoindole derivatives
US3935218A (en) * 1968-09-05 1976-01-27 American Home Products Corporation Imidazolinyl phenyl carbonyl compounds acid addition salts and related compounds
US3852303A (en) * 1969-03-05 1974-12-03 Sandoz Ag PROCESS FOR IMIDAZO{8 2,1-a{9 ISOINDOLES AND INTERMEDIATES
US3931218A (en) * 1973-02-14 1976-01-06 American Home Products Corporation 2-(N-alkyl-2-imidazolin-2-yl)benzophenones and process for their preparation
US3992400A (en) * 1974-04-04 1976-11-16 The Upjohn Company 1-(α-Phenyl-o-tolyl)imidazoles
US3936471A (en) * 1974-08-07 1976-02-03 American Home Products Corporation (Hexahydrobenzimidazol-2-yl)benzophenones and derivatives

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ES364423A1 (es) 1971-02-01
HU164902B (enrdf_load_stackoverflow) 1974-05-28
IL31580A0 (en) 1969-04-30
NO123530B (enrdf_load_stackoverflow) 1971-12-06
NL6902923A (enrdf_load_stackoverflow) 1969-09-09
IE32975L (en) 1970-09-07
IE32975B1 (en) 1974-02-06
IE33111B1 (en) 1974-03-20
CH541573A (de) 1973-09-15
CH503045A (de) 1971-02-15
IL39056A (en) 1973-01-30
DE1910932A1 (de) 1969-10-16
BR6906859D0 (pt) 1973-05-10
GB1187009A (en) 1970-04-08
DE1910933A1 (de) 1969-10-16
BE729433A (enrdf_load_stackoverflow) 1969-09-08
ES364424A1 (es) 1971-02-01
IE33111L (en) 1969-09-07
FR2070047B1 (enrdf_load_stackoverflow) 1974-01-11
IL31580A (en) 1973-01-30
GB1185618A (en) 1970-03-25
JPS4843757B1 (enrdf_load_stackoverflow) 1973-12-20
BE729432A (enrdf_load_stackoverflow) 1969-09-08
FR2003407A1 (enrdf_load_stackoverflow) 1969-11-07
HU162976B (enrdf_load_stackoverflow) 1973-05-28
CA948638A (en) 1974-06-04
NL6902846A (enrdf_load_stackoverflow) 1969-09-09
NO126084B (enrdf_load_stackoverflow) 1972-12-18
AT284112B (de) 1970-09-10
BR6906858D0 (pt) 1973-05-10
SE347511B (enrdf_load_stackoverflow) 1972-08-07
IL31558A0 (en) 1969-04-30
IL31558A (en) 1972-10-29
AT282623B (de) 1970-07-10
FR2070047A1 (enrdf_load_stackoverflow) 1971-09-10

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